Measures The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with
subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences
in pain-induced brain activation with and without controlling for HADS scores were evaluated.

Results Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered
rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with
rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior
midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal
cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation
in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively,
as confounding variables led to a loss of significant group differences.

Conclusions Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression,
which may modulate the affective–motivational aspects of the pain response.